Lanoxin

"The U.S. Food and Drug Administration today approved Entresto (sacubitril/valsartan) tablets for the treatment of heart failure. The drug has been shown to reduce the rate of cardiovascular death and hospitalization related to heart failure.

Lanoxin Injection

INDICATIONS

Heart Failure in Adults

LANOXIN is indicated for the
treatment of mild to moderate heart failure in adults. LANOXIN increases left
ventricular ejection fraction and improves heart failure symptoms, as evidenced
by improved exercise capacity and decreased heart failure-related
hospitalizations and emergency care, while having no effect on mortality. Where
possible, LANOXIN should be used in combination with a diuretic and an
angiotensin-converting enzyme (ACE) inhibitor.

Heart Failure in Pediatric
Patients

Atrial Fibrillation in Adults

LANOXIN is indicated for the
control of ventricular response rate in adult patients with chronic atrial fibrillation.

DOSAGE AND ADMINISTRATION

Important Dosing and Administration
Information

In selecting a LANOXIN dosing
regimen, it is important to consider factors that affect digoxin blood levels
(e.g., body weight, age, renal function, concomitant drugs) since toxic levels
of digoxin are only slightly higher than therapeutic levels. Dosing can be
either initiated with a loading dose followed by maintenance dosing if rapid
titration is desired or initiated with maintenance dosing without a loading
dose.

Parenteral administration of
digoxin should be used only when the need for rapid digitalization is urgent or
when the drug cannot be taken orally. Intramuscular injection can lead to
severe pain at the injection site, thus intravenous administration is
preferred. If the drug must be administered by the intramuscular route, it
should be injected deep into the muscle followed by massage. For adults, no
more than 500 mcg of LANOXIN Injection should be injected into a single site.
For pediatric patients, no more than 200 mcg of LANOXIN Injection Pediatric
should be injected into a single site.

Administer the dose over a
period of 5 minutes or longer and avoid bolus administration to prevent
systemic and coronary vasoconstriction. Mixing of LANOXIN Injection and
Injection Pediatric with other drugs in the same container or simultaneous
administration in the same intravenous line is not recommended.

LANOXIN Injection and Injection Pediatric can be
administered undiluted or diluted with a 4-fold or greater volume of Sterile
Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection.
The use of less than a 4-fold volume of diluent could lead to precipitation of
the digoxin. Immediate use of the diluted product is recommended.

If tuberculin syringes are used to measure very small
doses do not flush with the parenteral solution after its contents are expelled
into an indwelling vascularcatheter to avoid overadministration of digoxin.

Maintenance Dosing in Adults
and Pediatric Patients Over 10 Years Old

The recommended starting maintenance
doses in adults and pediatric patients over 10 years old with normal renal
function are given in Table 2. Doses may be increased every 2 weeks according
to clinical response, serum drug levels, and toxicity.

Table 3 provides the
recommended (once daily) maintenance dose for adults and pediatric patients
over 10 years old (to be given once daily) according to lean body weight and
renal function. The doses are based on studies in adult patients with heart
failure. Alternatively, the maintenance dose may be estimated by the following
formula (peak body stores lost each day through elimination):

Reduce the dose of LANOXIN in
patients whose lean weight is an abnormally small fraction of their total body
mass because of obesity or edema.

Table 3: Recommended Maintenance Dose (in micrograms
given once daily) of LANOXIN Injection in Pediatric Patients Over 10 Years Old
and Adults by Lean Body Weight and by Renal Function

Corrected Creatinine Clearancea

Lean Body Weightc

Number of Days Before Steady State Achievedb

kg

40

50

60

70

80

90

100

10 mL/min

64

80

96

112

128

144

160

19

20 mL/min

72

90

108

126

144

162

180

16

30 mL/min

80

100

120

140

160

180

200

14

40 mL/min

88

110

132

154

176

198

220

13

50 mL/min

96

120

144

168

192

216

240

12

60 mL/min

104

130

156

182

208

234

260

11

70 mL/min

112

140

168

196

224

252

280

10

80 mL/min

120

150

180

210

240

270

300

9

90 mL/min

128

160

192

224

256

288

320

8

100 mL/min

136

170

204

238

272

306

340

7

aFor adults, creatinine clearance was
corrected to 70-kg body weight or 1.73 m² body surface area. If only
serum creatinine concentrations (Scr) are available, a corrected Ccr may be
estimated in men as (140 – Age)/Scr. For women, this result should be
multiplied by 0.85. For pediatric patients, the modified Schwartz equation may be used. The
formula is based on height in cm and Scr in mg/dL where k is a constant. Ccr is
corrected to 1.73 m² body surface area. During the first year of
life, the value of k is 0.33 for pre-term babies and 0.45 for term infants. The
k is 0.55 for pediatric patients and adolescent girls and 0.7 for adolescent
boys.
GFR (mL/min/1.73 m²) = (k x Height)/ScrbIf no loading dose administered cThe doses listed assume average body composition.

Maintenance Dosing in Pediatric
Patients Less Than 10 Years Old

The starting maintenance dose
for heart failure in pediatric patients less than 10 years old is based on lean
body weight, renal function, age, and concomitant products [see CLINICAL
PHARMACOLOGY]. The recommended starting maintenance doses for pediatric patients
are given in Table 4. These recommendations assume the presence of normal renal
function.

Table 4: Recommended Starting LANOXIN Injection
Maintenance Dosage in Pediatric Patients Less Than 10 Years Old

Age

Dose Regimen, mcg/kg/dose (given TWICE daily)

Premature

1.9-3.1

Full-Term

3.0-4.5

1-24 Months

4.5-7.5

2-5 Years

3.8-53

5-10 Years

2.3-4.5

mcg = microgram

Table 5 provides average daily
maintenance dose requirements for pediatric patients less than 10 years old (to
be given twice daily) with heart failure based on age, lean body weight, and
renal function.

Table 5: Recommended
Maintenance Dose (in micrograms given TWICE daily) of LANOXIN Injection in
Pediatric Patients Less Than 10 Years of Agea Based upon Lean Body
Weight and Renal Functiona

Corrected Creatinine Clearanceb

Lean Body Weight

Number of Days Before Steady State Achievedc

kg

5

10

20

30

40

50

60

10 mL/min

8

16

32

48

64

80

96

19

20 mL/min

9

18

36

54

72

90

108

16

30 mL/min

10

20

40

60

80

100

120

14

40 mL/min

11

22

44

66

88

110

132

13

50 mL/min

12

24

48

72

96

120

144

12

60 mL/min

13

26

52

78

104

130

156

11

70 mL/min

14

28

56

84

112

140

168

10

80 mL/min

15

30

60

90

120

150

180

9

90 mL/min

16

32

64

96

128

160

192

8

100 mL/min

17

34

68

102

136

170

204

7

a Recommended are doses to be given twice daily. b The modified Schwartz equation may be used to estimate creatinine
clearance. See footnote a under Table 3. c If no loading dose administered.

Monitoring to Assess Safety,
Efficacy, and Therapeutic Blood Levels

Monitor for signs and symptoms
of digoxin toxicity and clinical response. Adjust dose based on toxicity,
efficacy, and blood levels.

Serum digoxin levels less than 0.5 ng/mL have been
associated with diminished efficacy, while levels above 2 ng/mL have been
associated with increased toxicity without increased benefit.

Interpret the serum digoxin concentration in the overall
clinical context, and do not use an isolated measurement of serum digoxin
concentration as the basis for increasing or decreasing the LANOXIN dose. Serum
digoxin concentrations may be falsely elevated by endogenous digoxin-like
substances [see DRUG INTERACTIONS]. If the assay is sensitive to these
substances, consider obtaining a baseline digoxin level before starting LANOXIN
and correct post-treatment values by the reported baseline level.

Obtain serum digoxin concentrations just before the next
scheduled LANOXIN dose or at least 6 hours after the last dose. The digoxin
concentration is likely to be 10-25% lower when sampled right before the next
dose (24 hours after dosing) compared to sampling 8 hours after dosing (using
once-daily dosing). However, there will be only minor differences in digoxin
concentrations using twice daily dosing whether sampling is done at 8 or 12
hours after a dose.

Switching from Intravenous Digoxin to Oral Digoxin

When switching from intravenous to oral digoxin
formulations, make allowances for differences in bioavailability when
calculating maintenance dosages (see Table 6).

Table 6: Comparison of the Systemic Availability and
Equivalent Doses of Oral and Intravenous LANOXIN